Response to letter to editor: 'Comment on Arch et al., Trials. 2016;17:517'

In October 2015 we published the paper ‘Measurement of HbA1c in multicentre diabetes trials – should blood samples be tested locally or sent to a central laboratory: an agreement analysis’. Chatterjee and Pradhan have submitted a letter to the editor asking critical questions regarding the methods we used. We offer this letter in response

Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10−7–10−5 M) of the specific β3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced comparable increases in intracellular cyclic AMP in CHOK1 cells transfected with the human β3-adrenoceptor to that obtained with isoprenaline (1 nM). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a β3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the β3-adrenoceptor showed a high affinity binding site with a Kd value 78±45 nM and a Bmax value (282±1 fmole mg protein−1) comparable with that of other β3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a β3-adrenoceptor

Exploring willingness of elder Chinese in Houston to participate in clinical research

AbstractBackground and objectivesInadequate minority participation in clinical research can threaten the applicability and strength of scientific findings. Previous research suggests that trial participation rates are lowest among Asian Americans, compared to other groups. This study explored barriers to clinical research participation among elder Chinese living in Houston, Texas. Additionally we administered the Trust in Medical Researchers Scale (TIMRS), used previously in researching trust in medical researchers as related to research participation.DesignIn this mixed methods study, a semi-structured interview, including the TIMRS were administered to 30 adults of Chinese ancestry aged 50 years or older recruited from a Chinese community center. Interviews were conducted in English, Mandarin and Cantonese and independently coded and analyzed using thematic content analysis. TIMRS scores were calculated for participants.ResultsParticipants were 70% female, 70% were 60 or elder, all were foreign born and on average lived in the US for 21.8 years. Participants perceived risks to research participation and preferred language concordant research staff. Interviewees were more willing to participate if they perceived personal and community health-related benefits. The overall TIMRS score was 23.9 (±5.0), lower than the overall TIMRS for Whites in a previous study (P < 0.001).ConclusionsThe barriers and facilitators to research participation confirmed previous research among Asians. Our participant TIMRS scores were consistent with decreased levels of trust observed in the original TIMRS study for African Americans as compared and lower than Whites. Employing strategies that utilize language concordant staff who build trust with participants may aid in recruiting elder Chinese, especially if the research is personally relevant to those being recruited

Determining optimal outcome measures in a trial investigating no routine gastric residual volume measurement in critically ill children

Background Choosing trial outcome measures is important. When outcomes are not clinically relevant or important to parents/patients, trial evidence is less likely to be implemented into practice. This study aimed to determine optimal outcome measures for a trial of no routine gastric residual volume measurement in critically ill children. Methods: A mixed methods approach: a focused literature review, parent and clinician interviews, a modified two-round Delphi and a stakeholder consensus meeting. Results: The review generated 13 outcomes. 14 Pediatric Intensive Care Unit (PICU) parents proposed 3 additional outcomes, these 16 were then rated by 28 clinicians in Delphi round 1. Six further outcomes were proposed, and 22 outcomes were rated in the second round. No items were voted ‘consensus out’. The 18 ‘no-consensus’ items were voted in a face-to-face meeting by 30 participants. The final 12 outcome measures were: Time to reach energy targets; ventilator associated pneumonia; vomiting; time enteral feeds withheld per 24 hour; necrotizing enterocolitis; length of invasive ventilation; PICU length of stay; mortality; change in weight and markers of feed intolerance: parenteral nutrition administered; feed formula altered and changing to post-pyloric feeds all secondary to feed intolerance. Conclusion: We have identified 12 outcomes for a trial of no gastric residual volume measurement through a multi-stage process, seeking views of parents and clinicians. Clinical Relevancy statement: Twelve relevant outcomes have been identified for a trial of no routine gastric residual volume measurement in critically ill children

State-of-the-art of spatial arch bridges

The paper describes a new form of bridge called a spatial arch bridge. This bridge type was developed in response to the demand for landmark structures, which have started to appear in the modern urban landscape to provide a symbol of originality, innovation and progress. Spatial arch bridges are defined as bridges in which the vertical deck loads produce bending moments and shear forces not contained in the arch plane, owing to their geometrical and structural configuration. Moreover, the arch itself may not be contained in a plane. The different variables and geometries that create such a structural configuration have been studied and classified. A wide compilation of examples of this bridge type has been made in chronological order, according to their construction date, from Maillarts first concrete spatial arch bridges to the latest designs and materials

Does an interactive trust-enhanced electronic consent improve patient experiences when asked to share their health records for research? A randomized trial

Objective In the context of patient broad consent for future research uses of their identifiable health record data, we compare the effectiveness of interactive trust-enhanced e-consent, interactive-only e-consent, and standard e-consent (no interactivity, no trust enhancement). Materials and Methods A randomized trial was conducted involving adult participants making a scheduled primary care visit. Participants were randomized into 1 of the 3 e-consent conditions. Primary outcomes were patient-reported satisfaction with and subjective understanding of the e-consent. Secondary outcomes were objective knowledge, perceived voluntariness, trust in medical researchers, consent decision, and time spent using the application. Outcomes were assessed immediately after use of the e-consent and at 1-week follow-up. Results Across all conditions, participants (N = 734) reported moderate-to-high satisfaction with consent (mean 4.3 of 5) and subjective understanding (79.1 of 100). Over 94% agreed to share their health record data. No statistically significant differences in outcomes were observed between conditions. Irrespective of condition, black participants and those with lower education reported lower satisfaction, subjective understanding, knowledge, perceived voluntariness, and trust in medical researchers, as well as spent more time consenting. Conclusions A large majority of patients were willing to share their identifiable health records for research, and they reported positive consent experiences. However, incorporating optional additional information and messages designed to enhance trust in the research process did not improve consent experiences. To improve poorer consent experiences of racial and ethnic minority participants and those with lower education, other novel consent technologies and processes may be valuable

Thermal stress induces glycolytic beige fat formation via a myogenic state.

Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival

Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population

Using increased trust in medical researchers to increase minority recruitment: The RECRUIT cluster randomized clinical trial

While extensive literature exists on barriers and strategies to increase minority participation in clinical trials, progress is limited. Few strategies were evaluated in randomized trials. We studied the impact of RECRUIT, a trust-based, cluster randomized minority recruitment trial layered on top of four traditional NIH-funded parent trials (BMT CTN, CABANA, PACES, STEADY-PD III; fifty specialty sites). RECRUIT was conducted from July 2013 through April 2017. Intervention sites implemented trust-based approaches customized to individual sites, promoting relationships between physician-investigators and minority-serving physicians and their minority patients. Control sites implemented only parent trials\u27 recruitment procedures. Adjusting for within-site clustering, we detected no overall intervention effect, odds ratio 1.3 (95% confidence limits 0.7,2.4). Heterogeneity among parent trials may have obscured the effect. Of the four parent trials, three enrolled more minorities in intervention versus control sites. CABANA odds ratio = 4.2 (adjusted 95%CL 1.5,11.3). PACES intervention sites enrolled 63% (10/16) minorities; control sites enrolled one participant in total, a minority, yielding an incalculable odds ratio. STEADY-PD III odds ratio = 2.2 (adjusted 95%CL 0.6,8.5). BMT CTN odds ratio \u3c 1, 0.8 (adjusted 95%CL 0.4,1.8). In conclusion, RECRUIT findings suggest the unique trust-based intervention increased minority recruitment to intervention trials in (3/4) of studied trials. Physician-investigators\u27 participation was critical to recruitment success. Lack of commitment to minority recruitment remained a barrier for some physician-investigators, especially in control sites. We recommend prospective physician investigators commit to minority recruitment activities prior to selection as site investigators and trial funding include some compensation for minority recruitment efforts.TRIAL REGISTRATION ClinicalTrials.govNCT01911208

Duration of intravenous antibiotic therapy for children with acute osteomyelitis or septic arthritis: a feasibility study.

BACKGROUND: There is little current consensus regarding the route or duration of antibiotic treatment for acute osteomyelitis (OM) and septic arthritis (SA) in children. OBJECTIVE: To assess the overall feasibility and inform the design of a future randomised controlled trial (RCT) to reduce the duration of intravenous (i.v.) antibiotic use in paediatric OM and SA. DESIGN: (1) A prospective service evaluation (cohort study) to determine the current disease spectrum and UK clinical practice in paediatric OM/SA; (2) a prospective cohort substudy to assess the use of targeted polymerase chain reaction (PCR) in diagnosing paediatric OM/SA; (3) a qualitative study to explore families' views and experiences of OM/SA; and (4) the development of a core outcome set via a systematic review of literature, Delphi clinician survey and stakeholder consensus meeting. SETTING: Forty-four UK secondary and tertiary UK centres (service evaluation). PARTICIPANTS: Children with OM/SA. INTERVENTIONS: PCR diagnostics were compared with culture as standard of care. Semistructured interviews were used in the qualitative study. RESULTS: Data were obtained on 313 cases of OM/SA, of which 218 (61.2%) were defined as simple disease and 95 (26.7%) were defined as complex disease. The epidemiology of paediatric OM/SA in this study was consistent with existing European data. Children who met oral switch criteria less than 7 days from starting i.v. antibiotics were less likely to experience treatment failure (9.6%) than children who met oral switch criteria after 7 days of i.v. therapy (16.1% when switch was between 1 and 2 weeks; 18.2% when switch was > 2 weeks). In 24 out of 32 simple cases (75%) and 8 out of 12 complex cases (67%) in which the targeted PCR was used, a pathogen was detected. The qualitative study demonstrated the importance to parents and children of consideration of short- and long-term outcomes meaningful to families themselves. The consensus meeting agreed on the following outcomes: rehospitalisation or recurrence of symptoms while on oral antibiotics, recurrence of infection, disability at follow-up, symptom free at 1 year, limb shortening or deformity, chronic OM or arthritis, amputation or fasciotomy, death, need for paediatric intensive care, and line infection. Oral switch criteria were identified, including resolution of fever for ≥ 48 hours, tolerating oral food and medicines, and pain improvement. LIMITATIONS: Data were collected in a 6-month period, which might not have been representative, and follow-up data for long-term complications are limited. CONCLUSIONS: A future RCT would need to recruit from all tertiary and most secondary UK hospitals. Clinicians have implemented early oral switch for selected patients with simple disease without formal clinical trial evidence of safety. However, the current criteria by which decisions to make the oral switch are made are not clearly established or evidence based. FUTURE WORK: A RCT in simple OM and SA comparing shorter- or longer-course i.v. therapy is feasible in children randomised after oral switch criteria are met after 7 days of i.v. therapy, excluding children meeting oral switch criteria in the first week of i.v. therapy. This study design meets clinician preferences and addresses parental concerns not to randomise prior to oral switch criteria being met. FUNDING: The National Institute for Health Research Health Technology Assessment programme